Irish Haemophilia Society, Dublin, Ireland; Trinity College, Dublin, Ireland.
The Division of Hematology, Oncology, and BMT at Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, Ohio, USA.
J Thromb Haemost. 2023 Dec;21(12):3450-3462. doi: 10.1016/j.jtha.2023.08.032. Epub 2023 Sep 6.
Severe hemophilia A (HA) negatively impacts health-related quality of life (HRQOL).
We aimed to analyze HRQOL in adult men with severe HA without inhibitors after valoctocogene roxaparvovec gene transfer in the phase 3 trial GENEr8-1.
Participant-reported outcomes were the hemophilia-specific quality of life questionnaire for adults (Haemo-QOL-A), the EQ-5D-5L instrument, the Hemophilia Activities List (HAL), and the Work Productivity and Activity Impairment Questionnaire: Hemophilia Specific (WPAI+CIQ:HS). Participants completed the questionnaires at baseline and through 104 weeks postinfusion with 6 × 10 vg/kg of valoctocogene roxaparvovec. Scores were analyzed per participant characteristics and outcomes.
For 132 HIV-negative participants, mean change from baseline in Haemo-QOL-A Total Score met the anchor-based clinically important difference (CID: 5.5) by week 12; the mean (SD) increase was 7.0 (12.6) at week 104. At week 104, improvement in Consequences of Bleeding, Treatment Concern, Worry, and Role Functioning domain scores exceeded the CID (6). EQ-5D-5L Utility Index scores improved above the CID at week 52, but not at week 104. EQ-5D-5L visual analog scale and HAL scores increased from baseline to week 104. Participants reported less activity and work impairment at week 104 than baseline. Participants with problem joints had lower mean baseline Haemo-QOL-A Total and domain scores than those without them, but improved over 104 weeks, except for 11 participants with ≥3 problem joints. Participants with 0 bleeds during the baseline prophylaxis period reported Haemo-QOL-A score improvements above the CID, including in the Consequences of Bleeding domain.
Valoctocogene roxaparvovec provided clinically meaningful HRQOL improvement for men with severe HA.
重型血友病 A（HA）会对健康相关生活质量（HRQOL）产生负面影响。
我们旨在分析在 3 期试验 GENEr8-1 中接受 valoctocogene roxaparvovec 基因转移治疗的无抑制剂的成年男性重型 HA 患者的 HRQOL。
参与者报告的结果为成人血友病特异性生活质量问卷（Haemo-QOL-A）、EQ-5D-5L 工具、血友病活动清单（HAL）和工作生产力和活动障碍问卷：血友病特定版（WPAI+CIQ:HS）。参与者在基线时和输注 6×10 vg/kg valoctocogene roxaparvovec 后 104 周内完成了这些问卷。根据参与者的特征和结果对评分进行了分析。
对于 132 名 HIV 阴性参与者，基线时 Haemo-QOL-A 总分的平均变化在第 12 周时符合基于锚定的临床重要差异（CID：5.5）；第 104 周时的平均（SD）增加为 7.0（12.6）。第 104 周时，出血后果、治疗顾虑、担忧和角色功能领域的评分改善超过 CID（6）。EQ-5D-5L 效用指数评分在第 52 周时改善超过 CID，但在第 104 周时没有。EQ-5D-5L 视觉模拟量表和 HAL 评分从基线增加到第 104 周。与基线相比，第 104 周时参与者的活动和工作障碍较少。有问题关节的参与者的 Haemo-QOL-A 总分和各领域的平均基线评分低于没有问题关节的参与者，但在 104 周内均有所改善，除了 11 名有≥3 个问题关节的参与者。在基线预防治疗期间无出血的参与者报告 Haemo-QOL-A 评分改善超过 CID，包括出血后果领域。
Valoctocogene roxaparvovec 为重型 HA 男性提供了具有临床意义的 HRQOL 改善。
